OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Humans ; Non-alcoholic Fatty Liver Disease ; Prospective Studies ; Risk Factors ; Exercise ; Liver

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective To investigate the effects of natural killer (NK)-cell-derived miR-30e-3p-containing exosomes (Exo) on esophageal squamous cell carcinoma (ESCC) cell proliferation, apoptosis and invasion. Methods NK cells were isolated and amplified from the peripheral blood of healthy donors, and NK cell-derived Exo was isolated and identified, which were further co-cultured with NEC cells and were randomly grouped into Exo1 and Exo2 groups. Transmission electron microscopy (TEM) was used to observe the morphology and size of exosomes. Western blot analysis was used to detect the expression levels of exosome markers apoptosis related gene 2- interacting protein X(ALIX), tumor susceptibility gene 101(TSG101), CD81 and calnexin. The NC plasmids, mimics and inhibitors of miR030e-3p were respectively delivered into the NK cells, and the corresponding NK cells-derived Exo were co-cultured with NEC cells, which were divided into NC, Exo, mimic and inhibitor groups. CCK-8 assay was used to evaluate cell proliferation, flow cytometry was conducted to determine cell cycle, annexin V-FITC/PI double staining was employed to detect cell apoptosis, and Transwell^TM assay was performed to detect cell invasion abilities. Real-time quantitative PCR was used to detect the expression of miR-23b, miR-422a, miR-133b, miR-124, miR-30e-3p and miR-99a in NCE cells and exosomes. Results The percentages of CD56⁺CD3⁺ cells and CD56⁺CD16⁺ cells in NK cells were (0.071±0.008)% and (90.6±10.6)%, respectively. Exosome isolated from NK cells ranged from 30 nm to 150 nm, and was positive for ALIX, TSG101 and CD81, while negative for calnexin. NK cell-derived Exos inhibited the proliferation, reduced the proportion of S-phase cells and the number of invaded cells of NEC cells, and promoted the apoptosis and the proportion of G1 phase cells. Overexpression of miR-30E-3p in NK cell-derived exosome inhibited the proliferation and invasion of NEC cells, and blocked cell cycle and promoted apoptosis, while knockdown miR-30e-3p in NK cell-derived exosomes did the opposite. Conclusion miR-30e-3p in NK cell-derived exosomes can inhibit the proliferation and invasion of ESCC cells, block their cell cycle and induce their apoptosis.
Humans ; Esophageal Squamous Cell Carcinoma/genetics* ; Esophageal Neoplasms/genetics* ; Exosomes/metabolism* ; Calnexin/metabolism* ; Cell Movement/genetics* ; MicroRNAs/metabolism* ; Cell Proliferation/genetics* ; Killer Cells, Natural ; Cell Line, Tumor ; Apoptosis/genetics*

OBJECTIVE: To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft. RESULTS: There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4⁺CD25⁺ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078). CONCLUSION High number of CD34⁺ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ cells tend to increase the occurrence of aGVHD, but high number of CD4⁺CD25⁺ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; CD4-Positive T-Lymphocytes ; Leukemia, Myeloid, Acute/complications* ; Graft vs Host Disease

OBJECTIVE: To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines. METHODS: Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy. RESULTS: Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G₀/G₁ phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified. CONCLUSION Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Wnt Signaling Pathway ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism* ; Apoptosis ; Drug Resistance, Multiple ; Membrane Proteins ; Cell Line, Tumor ; Cell Proliferation

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma/genetics* ; Mutation

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.
Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Humans ; Life Style ; Twins/genetics* ; Twins, Dizygotic ; Twins, Monozygotic

According to the taste analysis of Pudilan Xiaoyan Oral Liquid, the unpleasant taste of the oral liquid is mainly caused by the inherent taste of Chinese medicine and the taste introduced in the preparation process, which leads to its unpopularity among children. Therefore, aiming at the special children patient group, Xiaoer Pudilan Xiaoyan Syrup was developed via technology optimization and dosage form improvement to improve the unpleasant taste and enhance the medication compliance among children. Based on the material properties of Pudilan Xiaoyan Oral Liquid and Xiaoer Pudilan Xiaoyan Syrup extracts, the authors compared the properties(pH, density, turbidity, viscosity, chromaticity, particle size), taste, content of five quality markers and in vivo pharmacokinetic characteristics of these two preparations, to evaluate the suitability of Xiaoer Pudilan Xiaoyan Syrup. The results showed that compared with those of Pudilan Xiaoyan Oral Liquid, the pH, density, turbidity, viscosity and chromaticity of Xiaoer Pudilan Xiaoyan Syrup were significantly changed, and the unpleasant taste was reduced by 26%; the transfer rate of the main active ingredients chicoric acid was increased, while the transfer rate of baicalin had small difference from that of the oral liquid. In addition, pharmacokinetics revealed that the total absorption amount of baicalin in vivo was higher, and the time to peak T_(max) of baicalin and oroxindin in the syrup and the mean residence time MRT_(last )of corynoline in vivo were significantly prolonged. The absorption degree of Xiaoer Pudilan Xiaoyan Syrup and Pudilan Xiaoyan Oral Liquid in the body was the same: baicalin>oroxindin>corynoline. The new dosage form process was simpler than that of the original dosage form, safe, environmentally friendly, reasonable and feasible, meeting the mass production demand. This provided a basis for the reasonable and scientific optimization of Xiaoer Pudilan Xiaoyan Syrup, and also laid a foundation for its further safe and rational use, so as to expand the clinical application in children.
Child ; Humans ; Drugs, Chinese Herbal ; Glucuronates

Taking Pudilan Xiaoyan Oral Liquid as a demonstration, the effective delivery of quality markers in alcohol precipitation of Chinese medicine oral liquid preparations was studied. With the transfer rates of adenosine, corynoline, cichoric acid, baicalin, and wogonin as evaluation indexes, the effect of the density of concentrate before alcoholic precipitation, volume fraction of ethanol, stirring speed, temperature of concentrated solution, stirring time, alcohol concentration, alcohol precipitation time, alcoholic precipitation temperature, alcohol addition rate, and the pH of concentrate on the alcohol precipitation process was investigated by Plackett-Burman trial design, thus obtaining the key factors that influenced the alcohol precipitation process. The key factors were further optimized by Box-Behnken design to determine the optimal alcohol precipitation conditions. When the density of concentrate before alcoholic precipitation was 1.12 g·mL~(-1), the pH of concentrate was 6.86, and the alcohol concentration was 50.00%, the transfer rates of baicalin and wogonin were 91.86% and 87.78%, respectively. When the density of concentrate before alcoholic precipitation was 1.13 g·mL~(-1), the concentration of alcohol was 74.50%, and the alcoholic precipitation temperature was 17.0 ℃, the transfer rates of adenosine, corynoline, and cichoric acid were 85.95%, 71.62% and 83.19%, respectively. The method of optimizing alcohol precipitation techniques and determining the parameters of Pudilan Xiaoyan Oral Liquid by response surface methodology is reasonable and feasible, which provides guidance and experience for the effective delivery of quality markers in Chinese medicine oral liquid preparations.
Drugs, Chinese Herbal ; Ethanol ; Adenosine ; Chemical Precipitation